4.5 Article

Secreted IL-1α promotes T-cell activation and expansion of CD11b+Gr1+ cells in carbon tetrachloride-induced liver injury in mice

Journal

EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 45, Issue 7, Pages 2084-2098

Publisher

WILEY
DOI: 10.1002/eji.201445195

Keywords

Acute liver injury; CD11b(+)Gr1(+) myeloid cells; Membrane IL-1 alpha; Secreted IL-1 alpha; T-cell activation

Categories

Funding

  1. National Natural Science Foundation of China [81273268, 81102271]
  2. Suzhou city [SWG0904]
  3. Priority Academic Program Development of Jiangsu Higher Education Institutions
  4. Qing Lan project of Jiangsu Province
  5. Jiangsu Provincial Innovative Research Team
  6. Program for Changjiang Scholars and Innovative Research Team in University [IRT1075]

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Interleukin-1 alpha is mainly expressed on the cell membrane, but can also be secreted during inflammation. The roles of secreted and membrane IL-1 alpha in acute liver inflammation are still not known. Here, we examined the functions of secreted and membrane IL-1 alpha in a mouse model of carbon tetrachloride-induced acute liver injury. We show that secreted IL-1 alpha aggravates liver damage and membrane IL-1 alpha slightly protects mice from liver injury. Further studies showed that secreted IL-1 alpha promotes T-cell activation. It also increased the expansion of CD11b(+)Gr1(+) myeloid cells, which may serve as a negative regulator of acute liver inflammation. Moreover, secreted IL-1 alpha induced IL-6 production from hepatocytes. IL-6 neutralization reduced the proliferation of CD11b(+)Gr1(+) myeloid cells in vivo. CCL2 and CXCL5 expression was increased by secreted IL-1 alpha in vitro and in vivo. Antagonists of the chemokine receptors for CCL2 and CXCL5 significantly reduced the migration of CD11b(+)Gr1(+) myeloid cells. These results demonstrate that secreted and membrane IL-1 alpha play different roles in acute liver injury. Secreted IL-1 alpha could promote T-cell activation and the recruitment and expansion of CD11b(+)Gr1(+) myeloid cells through induction of CCL2, CXCL5, and IL-6. The controlled release of IL-1 alpha could be a critical regulator during acute liver inflammation.

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